{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:44:35Z","timestamp":1791499475974,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"\n Background<\/jats:title>\n Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1, 11\u03b2-HSD1) impair wound healing.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n Efficacy, safety, and feasibility of 11\u03b2-HSD1 inhibition for skin function and wound healing.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11\u03b2-HSD1 inhibitor AZD4017 (\n n<\/jats:italic>\n \u2009= 14) or placebo (\n n<\/jats:italic>\n \u2009= 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h\n ex vivo<\/jats:italic>\n skin 11\u03b2-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: \u22123.4 to 5.5) but reduced systemic 11\u03b2-HSD1 activity by 87% (69\u2013104%). Wound diameter was 34% (7\u201363%) smaller with AZD4017 at day 2, and 48% (12\u201385%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9\/month, 27\/28, and 95.3%, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers.<\/jats:p>\n <\/jats:sec>\n \n Significance statement<\/jats:title>\n Stress hormone activation by the enzyme 11\u03b2-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11\u03b2-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11\u03b2-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11\u03b2-HSD type 1 as a novel therapeutic target forchronic wounds.<\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/eje-21-1197","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T13:57:30Z","timestamp":1643896650000},"page":"441-455","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":21,"title":["Oral 11\u03b2-HSD1 inhibitor AZD4017 improves wound healing and skin integrity in adults with type 2 diabetes mellitus: a pilot randomized controlled trial"],"prefix":"10.1093","volume":"186","author":[{"given":"R A","family":"Ajjan","sequence":"first","affiliation":[{"name":"1Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-4755","authenticated-orcid":true,"given":"E M A","family":"Hensor","sequence":"additional","affiliation":[{"name":"2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"3NIHR Leeds Biomedical Research Center, Leeds Teaching Hospitals, NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Del Galdo","sequence":"additional","affiliation":[{"name":"2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"3NIHR Leeds Biomedical Research Center, Leeds Teaching Hospitals, NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Shams","sequence":"additional","affiliation":[{"name":"2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK"},{"name":"3NIHR Leeds Biomedical Research Center, Leeds Teaching Hospitals, NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Abbas","sequence":"additional","affiliation":[{"name":"1Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R J","family":"Fairclough","sequence":"additional","affiliation":[{"name":"4Emerging Innovations Unit, Discovery Sciences, BioPharmaceuticals R&D"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Webber","sequence":"additional","affiliation":[{"name":"5Emerging Portfolio Development, Late Oncology, Oncology R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Pegg","sequence":"additional","affiliation":[{"name":"5Emerging Portfolio Development, Late Oncology, Oncology R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Freeman","sequence":"additional","affiliation":[{"name":"4Emerging Innovations Unit, Discovery Sciences, BioPharmaceuticals R&D"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A E","family":"Taylor","sequence":"additional","affiliation":[{"name":"6Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK"},{"name":"7Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-9719","authenticated-orcid":true,"given":"W","family":"Arlt","sequence":"additional","affiliation":[{"name":"6Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK"},{"name":"7Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK"},{"name":"8NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A W","family":"Morgan","sequence":"additional","affiliation":[{"name":"1Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"},{"name":"3NIHR Leeds Biomedical Research Center, Leeds Teaching Hospitals, NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A","family":"Tahrani","sequence":"additional","affiliation":[{"name":"6Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK"},{"name":"7Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK"},{"name":"8NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P M","family":"Stewart","sequence":"additional","affiliation":[{"name":"3NIHR Leeds Biomedical Research Center, Leeds Teaching Hospitals, NHS Trust, Leeds, UK"},{"name":"9Faculty of Medicine and Health, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D A","family":"Russell","sequence":"additional","affiliation":[{"name":"1Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"},{"name":"10Leeds Vascular Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-2204","authenticated-orcid":true,"given":"A","family":"Tiganescu","sequence":"additional","affiliation":[{"name":"1Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK"},{"name":"3NIHR Leeds Biomedical Research Center, Leeds Teaching Hospitals, NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of 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